Etiological assessments of neurodegenerative dementias by in-vivo imaging of pathological protein aggregates in the brain

• Project/Area Number: 16H05324
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Higuchi Makoto 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, 部長(定常) (10373359)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
• Keywords: 認知症 / イメージング / 薬剤開発 / モデル動物 / 神経科学 / 薬理学 / 痴呆 / アルツハイマー病 / 前頭側頭葉変性症 / 生体イメージング

Outline of Final Research Achievements

The current study was aimed at visualizing all major hallmark pathologies of neurodegenerative dementias, consisting of fibrillary amyloid-beta, tau, alpha-synuclein, and TDP-43 protein aggregates, in the brains of living patients and animal models. Using original imaging agents for tau lesions, [11C]PBB3 and [18F]PM-PBB3, tau fibrils were found to accumulate in close association with clinical manifestations in Alzheimer’s disease, frontotemporal lobar degeneration, chronic traumatic encephalopathy, late-onset depression, and related disorders. The development of imaging probes for alpha-synuclein and TDP-43 pathologies made successful progress, yielding compounds that were immediately applicable to first-in-human PET studies. Notably, new imaging agents for alpha-synuclein deposits provided the first demonstration of in-vivo optical and PET imaging of disseminating alpha-synuclein fibrillization in rodent and non-human primate models.

Academic Significance and Societal Importance of the Research Achievements

アミロイドとタウ病変の生体脳イメージングにより、アルツハイマー病における両者の相互作用が示され、治療戦略上有用な情報が得られた。また、前頭側頭葉変性症や慢性外傷性脳症、高齢発症うつ病では、アミロイドよりもタウの沈着が発症や臨床症状に関連することが判明し、タウイメージングが診断や病勢評価に役立つ指標をもたらしうる。αシヌクレインおよびTDP-43病変プローブも臨床評価を開始できる段階まで開発が進み、世界に先駆けてヒトで病変の画像化が実現する可能性が高い。これにより、神経変性型認知症の100%近くを網羅する生体病理検査が可能になり、早期診断や治療介入ポイント決定に役立つ精密検査の実現が見込まれる。

Research Products

• [Int'l Joint Research] ペンシルバニア大学(米国)
• [Int'l Joint Research] カロリンスカ研究所(スウェーデン)
• [Int'l Joint Research] Mayo Clinic Jacksonville(米国)
• [Int'l Joint Research] University of British Columbia(カナダ)
• [Int'l Joint Research] University of British Columbia(カナダ)
• [Int'l Joint Research] University of Pennsylvania(米国)
• [Int'l Joint Research] CIC biomaGUNE(スペイン)
• [Int'l Joint Research] Nanyang Technological University(シンガポール)
• [Int'l Joint Research] Chang Gung University(台湾)
• [Int'l Joint Research] University of Pennsylvania/Mayo Clinic/NIH(米国)
• [Int'l Joint Research] University of British Columbia(Canada)
• [Int'l Joint Research] Karolinska Institutet(Sweden)
• [Int'l Joint Research] University of Ulm(Germany)
• [Journal Article] Excess tau PET ligand retention in elderly patients with major depressive disorder: a PET study (2020)
  • Author(s): Moriguchi Sho、（14名略）、Higuchi Makoto
  • Journal Title: Molecular Psychiatry Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Deschloroclozapine: a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys (2020)
  • Author(s): Nagai Yuji、（25名略）、Higuchi Makoto、Jian Jin、Bryan L. Roth、Minamimoto Takafumi
  • Journal Title: Nature Neuroscience Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Visualization of AMPA receptors in living human brain with positron emission tomography. (2020)
  • Author(s): Miyazaki T, Nakajima W, Hatano M, Shibata Y, Kuroki Y, Arisawa T, Mimura M, Yuzaki M, Kato H, Higuchi M, Uchida H, Takahashi T.
  • Journal Title: Nature Medicine Volume: 26 Issue: 2 Pages: 281-288
  • DOI: 10.1038/s41591-019-0723-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Selective Disruption of Inhibitory Synapses Leading to Neuronal Hyperexcitability at an Early Stage of Tau Pathogenesis in a Mouse Model. (2020)
  • Author(s): Shimojo M, Takuwa H, Takado Y, Tokunaga M, Tsukamoto S, Minatohara K, Ono M, Seki C, Maeda J, Urushihata T, Minamihisamatsu T, Aoki I, Kawamura K, Zhang MR, Suhara T, Sahara N, Higuchi M.
  • Journal Title: J Neurosci. Volume: 40 Issue: 17 Pages: 3491-3501
  • DOI: 10.1523/jneurosci.2880-19.2020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Staging of tau distribution by positron emission tomography may be useful in clinical staging of Alzheimer disease (2019)
  • Author(s): Kenta Aohara，Shinobu Minatani，Hiroko Kimura，Jun Takeuchi，Akitoshi Takeda，Joji Kawabe，Yasuhiro Wada，Aya Mawatari，Yasuyoshi Watanabe，Hitoshi Shimada，Makoto Higuchi，Tetsuya Suhara，Yoshiaki Itoh．
  • Journal Title: Neurology and Clinical Neurocience Volume: 8 Issue: 2 Pages: 61-67
  • DOI: 10.1111/ncn3.12366
  • NAID: 120007007732
  • URL: https://ocu-omu.repo.nii.ac.jp/records/2020114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Classification of Clinically Diagnosed Alzheimer's Disease Associated with Diabetes Based on Amyloid and Tau PET Results. (2019)
  • Author(s): Takenoshita N, Shimizu S, Kanetaka H, Sakurai H, Suzuki R, Miwa T, Odawara M, Ishii K, Shimada H, Higuchi M, Suhara T, Hanyu H
  • Journal Title: J Alzheimers Dis. Volume: 71 Issue: 1 Pages: 261-271
  • DOI: 10.3233/jad-190620
  • Peer Reviewed / Open Access
• [Journal Article] Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation (2019)
  • Author(s): Saito Takashi、Mihira Naomi、Matsuba Yukio、Sasaguri Hiroki、Hashimoto Shoko、Narasimhan Sneha、Zhang Bin、Murayama Shigeo、Higuchi Makoto、Lee Virginia M. Y.、Trojanowski John Q.、Saido Takaomi C.
  • Journal Title: Journal of Biological Chemistry Volume: 294 Issue: 34 Pages: 12754-12765
  • DOI: 10.1074/jbc.ra119.009487
  • Peer Reviewed / Open Access
• [Journal Article] PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury (2019)
  • Author(s): Takahata K、Kimura Yi、Sahara N、Koga S、Shimada H、Ichise M、Saito F、Moriguchi S、Kitamura S、Kubota M、Umeda S、Niwa F、Mizushima J、Morimoto Y、Funayama M、Tabuchi H、Bieniek K. F、Kawamura K、Zhang Ming-Rong、Dickson D. W、Mimura M、Kato M、Suhara T、Higuchi M
  • Journal Title: Brain Volume: 142 Issue: 10 Pages: 3265-3279
  • DOI: 10.1093/brain/awz238
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Design, Synthesis, and Evaluation of (4R)-1-{3-[2-(18F)Fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]pyrrolidin-2-one ([18F]T-401) as a Novel Positron-Emission Tomography Imaging Agent for Monoacylglycerol Lipase (2019)
  • Author(s): Hattori Yasushi、Aoyama Kazunobu、Maeda Jun、Arimura Naoto、Takahashi Yasuko、Sasaki Masako、Fujinaga Masayuki、Seki Chie、Nagai Yuji、Kawamura Kazunori、Yamasaki Tomoteru、Zhang Ming-Rong、Higuchi Makoto、Koike Tatsuki
  • Journal Title: Journal of Medicinal Chemistry Volume: 62 Issue: 5 Pages: 2362-2375
  • DOI: 10.1021/acs.jmedchem.8b01576
  • Peer Reviewed
• [Journal Article] Amyloid-Negative Dementia in the Elderly is Associated with High Accumulation of Tau in the Temporal Lobes (2019)
  • Author(s): Takeuchi Jun、Kikukawa Takayuki、Saito Haruna、Hasegawa Itsuki、Takeda Akitoshi、Hatsuta Hiroyuki、Kawabe Joji、Wada Yasuhiro、Mawatari Aya、Igesaka Ami、Doi Hisashi、Watanabe Yasuyoshi、Shimada Hitoshi、Kitamura Soichiro、Higuchi Makoto、Suhara Tetsuya、Itoh Yoshiaki
  • Journal Title: The Open Biomedical Engineering Journal Volume: 13 Issue: 1 Pages: 55-66
  • DOI: 10.2174/1874120701913010055
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In vivo binding of a tau imaging probe, [ 11 C]PBB3, in patients with progressive supranuclear palsy (2019)
  • Author(s): Endo Hironobu、Shimada Hitoshi、Sahara Naruhiko、Ono Maiko、Koga Shunsuke、Kitamura Soichiro、Niwa Fumitoshi、Hirano Shigeki、Kimura Yasuyuki、Ichise Masanori、Shinotoh Hitoshi、Zhang Ming Rong、Kuwabara Satoshi、Dickson Dennis W.、Toda Tatsushi、Suhara Tetsuya、Higuchi Makoto
  • Journal Title: Movement Disorders Volume: 34 Issue: 5 Pages: 744-754
  • DOI: 10.1002/mds.27643
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] First prototyping of a dedicated PET system with the hemisphere detector arrangement (2019)
  • Author(s): Tashima Hideaki、Yoshida Eiji、Iwao Yuma、Wakizaka Hidekatsu、Maeda Takamasa、Seki Chie、Kimura Yasuyuki、Takado Yuhei、Higuchi Makoto、Suhara Tetsuya、Yamashita Taichi、Yamaya Taiga
  • Journal Title: Physics in Medicine & Biology Volume: 64 Issue: 6 Pages: 065004-065004
  • DOI: 10.1088/1361-6560/ab012c
  • Peer Reviewed / Open Access
• [Journal Article] Clinical heterogeneity of frontotemporal dementia and Parkinsonism linked to chromosome 17 caused by MAPT N279K mutation in relation to tau positron emission tomography features (2019)
  • Author(s): Ikeda Aya、Shimada Hitoshi、Nishioka Kenya、Takanashi Masashi、Hayashida Arisa、Li Yuanzhe、Yoshino Hiroyo、Funayama Manabu、Ueno Yuji、Hatano Taku、Sahara Naruhiko、Suhara Tetsuya、Higuchi Makoto、Hattori Nobutaka
  • Journal Title: Movement Disorders Volume: 34 Issue: 4 Pages: 568-574
  • DOI: 10.1002/mds.27623
  • Peer Reviewed / Open Access
• [Journal Article] Tau imaging detects distinctive distribution of tau pathology in ALS/PDC on the Kii Peninsula (2018)
  • Author(s): Shinotoh Hitoshi、Shimada Hitoshi、Kokubo Yasumasa、Tagai Kenji、Niwa Fumitoshi、Kitamura Soichiro、Endo Hironobu、Ono Maiko、Kimura Yasuyuki、Hirano Shigeki、Mimuro Maya、Ichise Masanori、Sahara Naruhiko、Zhang Ming-Rong、Suhara Tetsuya、Higuchi Makoto
  • Journal Title: Neurology Volume: 92 Issue: 2
  • DOI: 10.1212/wnl.0000000000006736
  • Peer Reviewed / Open Access
• [Journal Article] Amyloid and Tau Positron Emission Tomography in Suggested Diabetesrelated Dementia (2018)
  • Author(s): Takenoshita Naoto、Fukasawa Raita、Ogawa Yusuke、Shimizu Soichiro、Umahara Takahiko、Ishii Kenji、Shimada Hitoshi、Higuchi Makoto、Suhara Tetsuya、Hanyu Haruo
  • Journal Title: Current Alzheimer Research Volume: 15 Issue: 11 Pages: 1062-1069
  • DOI: 10.2174/1567205015666180709113338
  • Peer Reviewed / Open Access
• [Journal Article] Microglial Activation During Pathogenesis of Tauopathy in rTg4510 Mice: Implications for the Early Diagnosis of Tauopathy. (2018)
  • Author(s): Naruhiko Sahara, Jun Maeda, Ai Ishikawa, Masaki Tokunaga, Tetsuya Suhara, Makoto Higuchi
  • Journal Title: Journal of Alzheimer's Disease Volume: 64 Issue: s1 Pages: S353-S359
  • DOI: 10.3233/jad-179933
  • Peer Reviewed
• [Journal Article] Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain (2018)
  • Author(s): Chiotis Konstantinos、Stenkrona Per、Almkvist Ove、Stepanov Vladimir、Ferreira Daniel、Arakawa Ryosuke、Takano Akihiro、Westman Eric、Varrone Andrea、Okamura Nobuyuki、Shimada Hitoshi、Higuchi Makoto、Halldin Christer、Nordberg Agneta
  • Journal Title: European Journal of Nuclear Medicine and Molecular Imaging Volume: 45 Issue: 9 Pages: 1605-1617
  • DOI: 10.1007/s00259-018-4012-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans (2018)
  • Author(s): Ito Takehito、Kimura Yasuyuki、Seki Chie、Ichise Masanori、Yokokawa Keita、Kawamura Kazunori、Takahashi Hidehiko、Higuchi Makoto、Zhang Ming-Rong、Suhara Tetsuya、Yamada Makiko
  • Journal Title: EJNMMI Research Volume: 8 Issue: 1 Pages: 48-48
  • DOI: 10.1186/s13550-018-0406-4
  • Peer Reviewed
• [Journal Article] Tau-induced focal neurotoxicity and network disruption related to apathy in Alzheimer’s disease (2018)
  • Author(s): Kitamura Soichiro、Shimada Hitoshi、Niwa Fumitoshi、Endo Hironobu、Shinotoh Hitoshi、Takahata Keisuke、Kubota Manabu、Takado Yuhei、Hirano Shigeki、Kimura Yasuyuki、Zhang Ming-Rong、Kuwabara Satoshi、Suhara Tetsuya、Higuchi Makoto
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: 89 Issue: 11 Pages: 1208-1214
  • DOI: 10.1136/jnnp-2018-317970
  • Peer Reviewed
• [Journal Article] Tau Fibril Formation in Cultured Cells Compatible with a Mouse Model of Tauopathy (2018)
  • Author(s): Matsumoto Gen、Matsumoto Kazuki、Kimura Taeko、Suhara Tetsuya、Higuchi Makoto、Sahara Naruhiko、Mori Nozomu
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 5 Pages: 1497-1497
  • DOI: 10.3390/ijms19051497
  • NAID: 120006988072
  • Peer Reviewed / Open Access
• [Journal Article] Water Diffusion in the Brain of Chronic Hypoperfusion Model Mice: A Study Considering the Effect of Blood Flow (2018)
  • Author(s): Urushihata Takuya、Takuwa Hiroyuki、 Seki Chie、 Tachibana Yasuhiko、Takahashi Manami、Jeff Kershaw、Takado Yuhei 、Aoki Ichio、Higuchi Makoto、Ito Hiroshi、Obata Takayuki
  • Journal Title: Magnetic Resonance in Medical Sciences Volume: 17 Issue: 4 Pages: 318-324
  • DOI: 10.2463/mrms.mp.2017-0149
  • NAID: 130007496873
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed / Open Access
• [Journal Article] Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease (2018)
  • Author(s): Hirano Shigeki、Shinotoh Hitoshi、Shimada Hitoshi、Ota Tsuneyoshi、Sato Koichi、Tanaka Noriko、Zhang Ming-Rong、Higuchi Makoto、Fukushi Kiyoshi、Irie Toshiaki、Kuwabara Satoshi、Suhara Tetsuya
  • Journal Title: Journal of Alzheimer's Disease Volume: 62 Issue: 4 Pages: 1539
  • DOI: 10.3233/jad-170749
  • URL: https://pure.teikyo.jp/en/publications/31f600f6-9031-4e0f-9f72-6080e89c19ea
  • Peer Reviewed
• [Journal Article] A human PET study of [11C]HMS011, a potential radioligand for AMPA receptors (2018)
  • Author(s): Keisuke Takahata et al.,
  • Journal Title: EJNMMI research Volume: 16 Issue: 1 Pages: 63-63
  • DOI: 10.1186/s13550-017-0313-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg4510 (2018)
  • Author(s): Ishikawa Ai、Tokunaga Masaki、Maeda Jun、Minamihisamatsu Takeharu、Shimojo Masafumi、Takuwa Hiroyuki、Ono Maiko、Ni Ruiqing、Hirano Shigeki、Kuwabara Satoshi、Ji Bin、Zhang Ming-Rong、Aoki Ichio、Suhara Tetsuya、Higuchi Makoto、Sahara Naruhiko
  • Journal Title: Journal of Alzheimer's Disease Volume: 61 Issue: 3 Pages: 1037-1052
  • DOI: 10.3233/jad-170509
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparative in-vitro quantification of pathological tau deposits and their association with neurodegeneration in tauopathy mouse models (2018)
  • Author(s): Ni R, Ji B, Ono M, Sahara N, Zhang M-R, Aoki I, Nordberg A, Suhara T, Higuchi M
  • Journal Title: J. Nuclear Medicine Volume: 117 Issue: 6 Pages: 960-966
  • DOI: 10.2967/jnumed.117.201632
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tau Filaments and the Development of Positron Emission Tomography Tracers (2018)
  • Author(s): Goedert Michel、Yamaguchi Yoshiki、Mishra Sushil K.、Higuchi Makoto、Sahara Naruhiko
  • Journal Title: Frontiers in Neurology Volume: 9 Pages: 70-70
  • DOI: 10.3389/fneur.2018.00070
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia (2018)
  • Author(s): Colas Lorena、Domercq Maria、Ramos-Cabrer Pedro、Palma Ana、Gomez-Vallejo Vanessa、Padro Daniel、Plaza-Garcia Sandra、Pulagam Krishna R.、Higuchi Makoto、Matute Carlos、Llop Jordi、Martin Abraham
  • Journal Title: Glia Volume: 66 Issue: 8 Pages: 1611-1624
  • DOI: 10.1002/glia.23326
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Imaging of Neuronal Activity in Awake Mice by Measurements of Flavoprotein Autofluorescence Corrected for Cerebral Blood Flow (2018)
  • Author(s): Takahashi Manami、Urushihata Takuya、Takuwa Hiroyuki、Sakata Kazumi、Takado Yuhei、Shimizu Eiji、Suhara Tetsuya、Higuchi Makoto、Ito Hiroshi
  • Journal Title: Frontiers in Neuroscience Volume: 11 Pages: 723-723
  • DOI: 10.3389/fnins.2017.00723
  • Peer Reviewed / Open Access
• [Journal Article] Fluorescence and autoradiographic evaluation of tau PET ligand PBB3 to a-synuclein pathology. (2017)
  • Author(s): Koga S, Ono M, Sahara N, Higuchi M, Dickson DW.
  • Journal Title: Movement Disorder Volume: - Issue: 6 Pages: 884-892
  • DOI: 10.1002/mds.27013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In Vivo Tau Imaging for a Diagnostic Platform of Tauopathy Using the rTg4510 Mouse Line (2017)
  • Author(s): Sahara Naruhiko、Shimojo Masafumi、Ono Maiko、Takuwa Hiroyuki、Febo Marcelo、Higuchi Makoto、Suhara Tetsuya
  • Journal Title: Frontiers in Neurology Volume: 8 Pages: 663-663
  • DOI: 10.3389/fneur.2017.00663
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High-contrast PET imaging of vasopressin V1B receptors with a novel radioligand, 11C-TASP699 (2017)
  • Author(s): Kazumi Koga, Yugi Nagai, Masayuki Hanyu, Mitsukane Yoshinaga, Shigeyuki Chaki, Norikazu Ohtake, Satoshi Ozaki, Ming-Rong Zhang, Tetsuya Suhara, Makoto HIguchi
  • Journal Title: Journal of Nuclear Medicine Volume: - Issue: 10 Pages: 1652-1658
  • DOI: 10.2967/jnumed.116.188698
  • Peer Reviewed
• [Journal Article] Affinity States of Striatal Dopamine D2 Receptors in Antipsychotic-Free Patients with Schizophrenia (2017)
  • Author(s): Kubota Manabu、Nagashima Tomohisa、Takano Harumasa、Kodaka Fumitoshi、Fujiwara Hironobu、Takahata Keisuke、Moriguchi Sho、Kimura Yasuyuki、Higuchi Makoto、Okubo Yoshiro、Takahashi Hidehiko、Ito Hiroshi、Suhara Tetsuya
  • Journal Title: International Journal of Neuropsychopharmacology Volume: 20 Issue: 11 Pages: 928-935
  • DOI: 10.1093/ijnp/pyx063
  • Peer Reviewed
• [Journal Article] Comparison between [ 18 F]fluorination and [ 18 F]fluoroethylation reactions for the synthesis of the PDE10A PET radiotracer [ 18 F]MNI-659 (2017)
  • Author(s): Mori Wakana、Takei Makoto、Furutsuka Kenji、Fujinaga Masayuki、Kumata Katsushi、Muto Masatoshi、Ohkubo Takayuki、Hashimoto Hiroki、Tamagnan Gilles、Higuchi Makoto、Kawamura Kazunori、Zhang Ming-Rong
  • Journal Title: Nuclear Medicine and Biology Volume: 55 Pages: 12-18
  • DOI: 10.1016/j.nucmedbio.2017.08.002
  • Peer Reviewed
• [Journal Article] Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in living human brain. (2017)
  • Author(s): Ishii T, Kimura Y, Ichise M, Takahata K, Kitamura S, Moriguchi S, Kubota M, Zhang MR, Yamada M, Higuchi M, Okubo Y, Suhara T.
  • Journal Title: PLoS One. Volume: 12 Issue: 12 Pages: e0189318-e0189318
  • DOI: 10.1371/journal.pone.0189318
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A migration case of Kii amyotrophic lateral sclerosis/parkinsonism dementia complex with the shortest stay in the endemic area and the longest incubation to develop the disease (2017)
  • Author(s): Tsunoda Keiichiro、Yamashita Toru、Shimada Hitoshi、Nomura Emi、Takahashi Yoshiaki、Shang Jingwei、Sato Kota、Takemoto Mami、Hishikawa Nozomi、Ohta Yasuyuki、Higuchi Makoto、Suhara Tetsuya、Kokubo Yasumasa、Kuzuhara Shigeki、Abe Koji
  • Journal Title: Journal of Clinical Neuroscience Volume: 46 Pages: 64-67
  • DOI: 10.1016/j.jocn.2017.08.057
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2 (2017)
  • Author(s): Moriguchi Sho、Takano Harumasa、Kimura Yasuyuki、Nagashima Tomohisa、Takahata Keisuke、Kubota Manabu、Kitamura Soichiro、Ishii Tatsuya、Ichise Masanori、Zhang Ming-Rong、Shimada Hitoshi、Mimura Masaru、Meyer Jeffrey H、Higuchi Makoto、Suhara Tetsuya
  • Journal Title: International Journal of Neuropsychopharmacology Volume: 20 Issue: 12 Pages: 957-962
  • DOI: 10.1093/ijnp/pyx069
  • Peer Reviewed / Open Access
• [Journal Article] PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins (2017)
  • Author(s): Perez-Soriano Alexandra、Arena Julieta E.、Dinelle Katie、Miao Qing、McKenzie Jessamyn、Neilson Nicole、Puschmann Andreas、Schaffer Paul、Shinotoh Hitoshi、Smith-Forrester Jenna、Shahinfard Elham、Vafai Nasim、Wile Daryl、Wszolek Zbigniew、Higuchi Makoto、Sossi Vesna、Stoessl A. Jon
  • Journal Title: Movement Disorders Volume: 32 Issue: 7 Pages: 1016-1024
  • DOI: 10.1002/mds.27029
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male (2017)
  • Author(s): Barron Anna M.、Ji Bin、Kito Seiji、Suhara Tetsuya、Higuchi Makoto
  • Journal Title: Biochemical Journal Volume: 475 Issue: 1 Pages: 75-85
  • DOI: 10.1042/bcj20170645
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between Aβ and tau accumulations and their influence on clinical features in aging and Alzheimer’s disease spectrum brains: A [11C]PBB3-PET study (2017)
  • Author(s): Shimada H, Kitamura S, Shinoto H, Endo H, Niwa F, Hirano, S Zhang M-R, Suhara T, Higuchi M
  • Journal Title: Alzheimer’s & Dementia (Amst) Volume: 6 Issue: 1 Pages: 11-20
  • DOI: 10.1016/j.dadm.2016.12.009
  • Peer Reviewed / Open Access
• [Journal Article] Propagation of pathological α-synuclein in marmoset brain (2017)
  • Author(s): Aki Shimozawa, Maiko Ono, Daisuke Takahara, Airi Tarutani, Sei Imura, Masami Masuda-Suzukake, Makoto Higuchi, Kazuhiko Yanai, Shin-ichi Hisanaga, Masato Hasegawa
  • Journal Title: Acta Neuropathologica Communications Volume: 5 Issue: 1 Pages: 12-14
  • DOI: 10.1186/s40478-017-0413-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Distinct binding of two PET ligands, PBB3 and AV-1451, to tau fibril strains in Alzheimer’s disease and related neurodegenerative tauopathy disorders. (2017)
  • Author(s): 71.Ono M, Sahara N, Kumata K, Ji B, Ni R, Dickson DW, Trojanowski JQ, Lee VM-Y, Yoshida M, Hozumi I, Yoshiyama Y, Nordberg A, Suhara T, Zhang M-R, Higuchi M.
  • Journal Title: Brain Volume: 140 Pages: 764-780
  • DOI: 10.1093/brain/aww339
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Measurement of psychological state changes at low dopamine transporter occupancy following a clinical dose of mazindol (2017)
  • Author(s): Yasuyuki Kimura, Jun Maeda, Makiko Yamada, Keisuke Takahata, Keita Yokokawa, Yoko Ikoma, Chie Seki, Hiroshi Ito, Makoto Higuchi, Tetsuya Suhara
  • Journal Title: Psychopharmacology Volume: 234 Issue: 3 Pages: 323-328
  • DOI: 10.1007/s00213-016-4464-x
  • Peer Reviewed
• [Journal Article] DREADD-expressing neurons in living brain and their application to implantation of iPSC-derived neuroprogenitors. (2016)
  • Author(s): Ji B, Kaneko H, Minamimoto T, Inoue H, Takeuchi H, Kumata K, Zhang MR, Aoki I, Seki C, Ono M, Tokunaga M, Tsukamoto S, Tanabe K, Shin RM, Minamihisamatsu T, Kito S, Richmond BJ, Suhara T, Higuchi M.
  • Journal Title: J. Neuroscience Volume: 36 Issue: 45 Pages: 11544-11558
  • DOI: 10.1523/jneurosci.1279-16.2016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Calcium dysregulation contributes to neurodegeneration in FTLD patient iPSC-derived neurons (2016)
  • Author(s): Imamura, K., Sahara, N., Kanaan, N. M., Tsukita, K., Kondo, T., Kutoku, Y., Ohsawa, Y., Sunada, Y., Kawakami, K., Hotta, A., Yawata, S., Watanabe, D., Hasegawa, M., Trojanowski, J. Q., Lee, V. M.-Y., Suhara, T., Higuchi, M., and Inoue, H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 34904-34904
  • DOI: 10.1038/srep34904
  • NAID: 120005850272
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Assessment of neuroinflammation in a mouse model of obesity and β-amyloidosis using PET (2016)
  • Author(s): Barron A, Tokunaga M, Zhang M-R, Bin Ji, Suhara T, Higuchi M
  • Journal Title: Journal of Neuroinflammation Volume: 13 Issue: 1 Pages: 221-221
  • DOI: 10.1186/s12974-016-0700-x
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis and preclinical evaluation of sulfonamido-based [11C-Carbonyl]-carbamates and ureas for imaging monoacylglycerol lipase. (2016)
  • Author(s): Wang L, Mori W, Cheng R, Yui J, Hatori A, Ma L, Zhang Y, Rotstein BH, Fujinaga M, Shimoda Y, Yamasaki T, Xie L, Nagai Y, Minamimoto T, Higuchi M, Vasdev N, Zhang MR, Liang SH.
  • Journal Title: Theranostics Volume: 6(8) Issue: 8 Pages: 1145-1159
  • DOI: 10.7150/thno.15257
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Imaging neural and glial pathways and their functions in homeostasis and pathogenesis (2020)
  • Author(s): Higuchi Makoto
  • Organizer: The 10th Niigata University Brain Research Institute International Symposium
  • Int'l Joint Research / Invited
• [Presentation] Tau imaging (2020)
  • Author(s): Higuchi Makoto
  • Organizer: The 18th Conference of Peace through Mind/Brain Science
  • Int'l Joint Research / Invited
• [Presentation] In-vivo assessments of protein fibrillogenesis, oxidative stress, and reactive gliosis (2020)
  • Author(s): Higuchi Makoto
  • Organizer: The 8th International Symposium of Gunma University Initiative for Advanced Research
  • Int'l Joint Research / Invited
• [Presentation] In Vivo Optical and PET Imaging of Disseminating Alpha-synuclein Pathologies in Animal Models (2019)
  • Author(s): Higuchi Makoto
  • Organizer: Michael J. Fox Foundation alpha-Synuclein Imaging Summit
  • Int'l Joint Research / Invited
• [Presentation] Future Molecular Imaging Techniques in Neurodegenerative Diseases (2019)
  • Author(s): Higuchi Makoto
  • Organizer: 2019 International Conference of Korean Movement Disorder Society
  • Int'l Joint Research / Invited
• [Presentation] グリアリンパ系と脳内ミエロイドリレー： 新たに発見された脳内インフラの役割 (2019)
  • Author(s): 樋口真人
  • Organizer: 第92回日本生化学会大会
  • Invited
• [Presentation] 認知症の診断・治療へ貢献する核医学イメージングの新展開 (2019)
  • Author(s): 樋口真人
  • Organizer: 日本核医学会近畿地方会
  • Invited
• [Presentation] Imaging of tau pathologies with PBB3 and its fluorinated derivatives (2019)
  • Author(s): Higuchi Makoto
  • Organizer: Molecular Imaging Analysis on Brain Disorders - Fukui 2019
  • Int'l Joint Research / Invited
• [Presentation] Roles of astrocytes in Alzheimer's disease revealed by multiscale in vivo imaging (2019)
  • Author(s): Higuchi Makoto
  • Organizer: International Symposium on Reactive Astrocytes and Alzheimer's Disease of The Brain Research Program
  • Int'l Joint Research / Invited
• [Presentation] Novel homeostatic function of glial cells in health and disease (2019)
  • Author(s): Higuchi Makoto
  • Organizer: 第60回日本神経学会学術集会
  • Int'l Joint Research / Invited
• [Presentation] Updates on PET imaging of tau pathologies (2019)
  • Author(s): Higuchi Makoto
  • Organizer: 第60回日本神経学会学術集会
  • Int'l Joint Research / Invited
• [Presentation] Visualization of proteinopathies in Alzheimer's disease and allied neurodegenerative disorders (2018)
  • Author(s): 樋口真人
  • Organizer: KSCPT-JSCPT Joint Symposium
  • Int'l Joint Research / Invited
• [Presentation] Imaging Molecular Pathologies of Alzheimer's Disease and Related Neurodegenerative Disorders (2018)
  • Author(s): 樋口真人
  • Organizer: International Alzheimer's Disease Conference
  • Int'l Joint Research / Invited
• [Presentation] Molecular imaging for diagnosis and treatment of neurodegenerative disorders at a prodromal stage (2018)
  • Author(s): 樋口真人
  • Organizer: 18th World Congress of Basic and Clinical Pharmacology (WCP2018)
  • Int'l Joint Research / Invited
• [Presentation] Imaging of tau pathologies and tau-induced neurodegeneration (2018)
  • Author(s): 樋口真人，島田斉，須原哲也
  • Organizer: 2018 International Conference on Neurodegenerative Disorders
  • Int'l Joint Research / Invited
• [Presentation] Molecular imaging of Alzheimer's disease and related disorders (2018)
  • Author(s): 樋口真人
  • Organizer: The 32nd Korean Academy of Science and Technology International Symposium
  • Int'l Joint Research / Invited
• [Presentation] Tau PET Ligands (2018)
  • Author(s): 樋口真人
  • Organizer: MDS-AOS Neuroimaging Course
  • Int'l Joint Research / Invited
• [Presentation] New Frontiers in Molecular Imaging (2018)
  • Author(s): 樋口真人
  • Organizer: The 22nd International Congress of Parkinson's Disease and Movement Disorders
  • Int'l Joint Research / Invited
• [Presentation] 精神神経疾患の分子病態イメージング (2018)
  • Author(s): 樋口真人
  • Organizer: 第28回東京臨床脳画像解析研究会
  • Invited
• [Presentation] Imaging of neuropathology and functional disruptions in neurodegenerative dementias (2018)
  • Author(s): 樋口真人
  • Organizer: UK-Japan Neuroscience Symposium
  • Int'l Joint Research / Invited
• [Presentation] 神経変性疾患病理の生体イメージング (2017)
  • Author(s): 樋口真人
  • Organizer: 第13回パーキンソン病臨床懇話会
  • Place of Presentation: 埼玉県さいたま市
  • Year and Date: 2017-12-02
  • Invited
• [Presentation] Neurodegenerative dementias as proteinopathies (2017)
  • Author(s): 樋口真人
  • Organizer: Brain Networks: From Molecules To Diseases, Neuroscience and Mental Health
  • Place of Presentation: Singapore
  • Year and Date: 2017-03-17
  • Int'l Joint Research / Invited
• [Presentation] Imaging-Pathological Correlations of Parkinson’s Disease (2017)
  • Author(s): 樋口真人
  • Organizer: The 21th International Congress of Parkinson's Disease and Movement Disorders
  • Int'l Joint Research / Invited
• [Presentation] Current status in development of next generation tau ligands (2017)
  • Author(s): 島田斉、樋口真人
  • Organizer: International Tau Symposium 2017
  • Int'l Joint Research / Invited
• [Presentation] Imaging tau with 11C-PBB3 and its 18F derivatives (2017)
  • Author(s): 樋口真人
  • Organizer: The 30th Annual Congress of the European Association of Nuclear Medicine
  • Int'l Joint Research / Invited
• [Presentation] 認知症の克服に向けた核医学の貢献 (2016)
  • Author(s): 樋口真人, 島田斉, 木村泰之, 佐原成彦, 堀口隆司, 須原哲也
  • Organizer: 第56回日本核医学会学術総会・第36回日本核医学技術学会総会学術大会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2016-10-26
  • Invited
• [Presentation] 放射線応答と認知障害をつなぐ 神経免疫細胞のイメージング (2016)
  • Author(s): 樋口真人
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: 広島県広島市
  • Year and Date: 2016-10-26
• [Presentation] PBB3 in AD and non-AD tauopathies (2016)
  • Author(s): 樋口真人
  • Organizer: Tau PET Futures Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-10-14
  • Int'l Joint Research / Invited
• [Presentation] Development of PBB3 (2016)
  • Author(s): 樋口真人
  • Organizer: Tau PET Futures Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-10-13
  • Int'l Joint Research / Invited
• [Presentation] アルツハイマー病の臨床診断 ～画像検査とバイオマーカー～ (2016)
  • Author(s): 樋口真人
  • Organizer: 第46回日本神経精神薬理学会年会
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-07-03
  • Invited
• [Presentation] 変性型認知症の分子イメージング (2016)
  • Author(s): 樋口真人, 島田斉, 田桑弘之, 佐原成彦, 須原哲也
  • Organizer: 第46回日本神経精神薬理学会年会
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-07-02
  • Invited
• [Presentation] タウ病変の生体イメージング (2016)
  • Author(s): 樋口真人
  • Organizer: Stroke 2016
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2016-04-15
  • Invited
• [Presentation] 認知症タウイメージングの進歩 (2016)
  • Author(s): 樋口真人
  • Organizer: 第2回東西合同脳神経外科認知症研究会
  • Place of Presentation: 東京都
  • Year and Date: 2016-04-09
  • Invited
• [Remarks] 脳機能イメージング研究部 脳疾患トランスレーショナル研究チーム
  • URL: http://www.nirs.qst.go.jp/seika/brain/team/molecular_08.html
• [Remarks] 平成30年度文部科学大臣表彰科学技術賞を受賞
  • URL: http://www.qst.go.jp/information/itemid047-003998.html
• [Remarks] 脳機能イメージング研究部
  • URL: http://www.nirs.qst.go.jp/seika/brain/index.html
• [Patent(Industrial Property Rights)] αシヌクレイン凝集体結合剤及びイメージング方法 (2020)
  • Inventor(s): 樋口真人, 小野麻衣子, 須原哲也, 張明栄
  • Industrial Property Rights Holder: 樋口真人, 小野麻衣子, 須原哲也, 張明栄
  • Industrial Property Rights Type: 特許
  • Filing Date: 2020
  • Overseas
• [Patent(Industrial Property Rights)] αシヌクレイン凝集体結合剤及びイメージング方法 (2019)
  • Inventor(s): 樋口真人、小野麻衣子、須原哲也、張明栄
  • Industrial Property Rights Holder: 量子科学技術研究開発機構
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
• [Patent(Industrial Property Rights)] 四足動物保定装置 (2017)
  • Inventor(s): 樋口真人、田桑弘之、高堂裕平、漆畑拓弥
  • Industrial Property Rights Holder: 量子科学技術研究開発機構
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-164080
  • Filing Date: 2017